TY - JOUR
T1 - Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
AU - Brahmer, Julie R.
AU - Tykodi, Scott S.
AU - Chow, Laura Q.M.
AU - Hwu, Wen Jen
AU - Topalian, Suzanne L.
AU - Hwu, Patrick
AU - Drake, Charles G.
AU - Camacho, Luis H.
AU - Kauh, John
AU - Odunsi, Kunle
AU - Pitot, Henry C.
AU - Hamid, Omid
AU - Bhatia, Shailender
AU - Martins, Renato
AU - Eaton, Keith
AU - Chen, Shuming
AU - Salay, Theresa M.
AU - Alaparthy, Suresh
AU - Grosso, Joseph F.
AU - Korman, Alan J.
AU - Parker, Susan M.
AU - Agrawal, Shruti
AU - Goldberg, Stacie M.
AU - Pardoll, Drew M.
AU - Gupta, Ashok
AU - Wigginton, Jon M.
PY - 2012/6/28
Y1 - 2012/6/28
N2 - Background: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. Methods: In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. Results: As of February 24, 2012, a total of 207 patients - 75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer - had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. Conclusions: Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.)
AB - Background: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. Methods: In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. Results: As of February 24, 2012, a total of 207 patients - 75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer - had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. Conclusions: Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.)
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U2 - 10.1056/NEJMoa1200694
DO - 10.1056/NEJMoa1200694
M3 - Article
C2 - 22658128
AN - SCOPUS:84862903106
SN - 0028-4793
VL - 366
SP - 2455
EP - 2465
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 26
ER -